This dataset comprises in vivo experiments performed in male Sprague-Dawley rats treated daily with sodium nitrite (15 mg/kg by gavage) and/or omeprazole (10 mg/kg intraperitoneally) for 1,7 or 14 days. Six hours after the last nitrite administration, animals were euthanized and samples of blood and tissues (aorta, muscle, liver, heart, and brain) were collected. The dataset includes biochemical and molecular measurements of nitrite, nitrate, RxNO (reactive nitrosated species), RSNO (S-nitrosothiols), non-protein thiol (NPT) content, expression of antioxidant defense genes (e.g., Mgst1, Hmox1, Keap1, Nfe2l2), activity of oxidative stress-related enzymes (XOR, GPx, SOD, catalase), generation of reactive oxygen species (superoxide, hydrogen peroxide), and classical plasma markers of hepatic injury (AST, ALT, LDH). The dataset consists of quantitative biochemical and molecular data obtained using the following analytical techniques: Gas-phase chemiluminescence for nitrite, nitrate, RxNO, and RSNO quantification; Spectrophotometric and fluorimetric assays for thiol content, peroxide levels, total antioxidant capacity (DPPH), and oxidative stress enzyme activity; RT-qPCR for gene expression analysis of antioxidant defense systems; Enzymatic assays for XOR, GPx, SOD, and catalase activities, and for ROS production; Clinical biochemistry assays for AST, ALT, and LDH in plasma and tissues. The primary goal of this dataset is to investigate the pharmacological interaction between orally administered nitrite and the proton pump inhibitor omeprazole, focusing on nitric oxide (NO) metabolism, redox homeostasis, and tissue oxidative stress. Specifically, the dataset enables the examination of: how nitrite treatment alters NO-related metabolites across different tissues and plasma; whether omeprazole modulates these NO-metabolite patterns and influences tissue redox balance; the relationship between these biochemical changes, antioxidant gene expression, and hepatic toxicity markers. Overall, these data provide mechanistic insight into the dual redox-modulating effects of nitrite and omeprazole, contributing to the understanding of NO-based pharmacology and redox biology. Making these data available enhances transparency, reproducibility, and opportunities for secondary analyses in fields such as nitric oxide metabolism, pharmacology, biochemistry, and toxicology.